DNP and DNP prodrug treatment of neuromuscular, neurodegenerative, autoimmune, developmental, traumatic brain injury, concussion, dry eye disease, hearing loss and/or metabolic diseases

Patent metadata

Field	Value
Publication number	US-11406642-B2
Application number	US-201916695653-A
Country	US
Kind code	B2
Filing date	Nov 26, 2019
Priority date	Mar 7, 2016
Publication date	Aug 9, 2022
Grant date	Aug 9, 2022

Abstract

A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment.

First claim

We claim:

1. A method of treatment of multiple sclerosis (MS), traumatic brain injury (TBI), and Parkinson's disease, comprising:
administering to a patient in need of treatment a dose of a composition comprising a dinitrophenol prodrug of formula II,
wherein the dose of the dinitrophenol prodrug of formula II is: from about 0.01 mg/kg of body weight to about 25 mg/kg of body weight of the patient in need of treatment; or from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment,
wherein in formula II:

R is selected from the group of substituents in Table A, and:

TABLE A

Assignees

• Mitochon Pharmaceuticals Inc
• Bioventures Llc

Inventors

• Geisler John Gerard
• Alonso Robert
• Crooks Peter Anthony
• Penthala Narsimha Reddy
• Albayati Zaineb

Classifications

• C07D295/205

  Radicals derived from carbonic acid · CPC title

• A61K31/06 Primary

  the aromatic ring being substituted by nitro groups · CPC title

• A61K31/27

  of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61K31/221

  with compounds having an amino group, e.g. acetylcholine, acetylcarnitine · CPC title